Tuesday, 29 May 2018

An article
published this year in “Journal of
International Natural Products” using one of our products,“FITC Apoptosis
Detection Kit”, by our customers fromtheCRIOBE,
USR CNRS-EPHE-UPVD, Universitéde Perpignan, France and Universidad de Santiago
de Compostela, Lugo, Spain in how Structures
and Activities of Tiahuramides A−C, Cyclic Depsipeptides from a Tahitian
Collection of the Marine Cyanobacterium Lyngbya majuscula. Congrats and
Thanks.

Summay:

The structures of three new cyclic depsipeptides, tiahuramides A (1), B
(2), and C (3), from a French Polynesian collection of the marine
cyanobacterium Lyngbya majuscula are described. The planar structures of these
compounds were established by a combination of mass spectrometry and 1D and 2D
NMR experiments. Absolute configurations of natural and nonproteinogenic amino
acids were determined through a combination of acid hydrolysis, derivitization
with Marfey’s reagent, and HPLC. The absolute configuration of hydroxy acids
was confirmed by Mosher’s method. The antibacterial activities of tiahuramides
against three marine bacteria were evaluated. Compound 3 was the most active
compound of the series, with an MIC of 6.7 μM on one of
the three tested bacteria. The three peptides inhibit the first cell division
of sea urchin fertilized eggs with IC50 values in the range from 3.9 to 11 μM. Tiahuramide B (2), the most potent compound, causes cellular
alteration characteristics of apoptotic cells, blebbing, DNA condensation, and
fragmentation, already at the first egg cleavage. The cytotoxic activity of
compounds 1−3 was tested in SH-SY5Y human neuroblastoma cells. Compounds 2 and
3 showed an IC50 of 14 and 6.0 μM, respectively,
whereas compound 1 displayed no toxicity in this cell line at 100 μM. To determine the type of cell death induced by tiahuramide C (3),
SH-SY5Y cells were costained with annexin V−FITC and propidium iodide and
analyzed by flow cytometry. The double staining indicated that the cytotoxicity
of compound 3 in this cell line is produced by necrosis.

Cholesterol
metabolism is crucial for cells and, in particular, its biosynthesis in the
central nervous system occurs in situ, and its deregulation involves
morphological changes that cause functional variations and trigger programmed
cell death. The pathogenesis of rare diseases, such as Mevalonate Kinase
Deficiency or Smith–Lemli–Opitz Syndrome, arises due to enzymatic defects in
the cholesterol metabolic pathways, resulting in a shortage of downstream
products. The most severe clinical manifestations of these diseases appear as
neurological defects. Expanding the knowledge of this biological mechanism will
be useful for identifying potential targets and preventing neuronal damage.
Several studies have demonstrated that deregulation of the cholesterol pathway
induces mitochondrial dysfunction as the result of respiratory chain damage. We
set out to determine whether mitochondrial damage may be prevented by using
protective mitochondria-targeted compounds, such as MitoQ, in a neuronal cell
line treated with a statin to induce a biochemical block of the cholesterol
pathway. Evidence from the literature suggests that mitochondria play a crucial
role in the apoptotic mechanism secondary to blocking the cholesterol pathway.
Our study shows that MitoQ, administered as a preventive agent, could counteract
the cell damage induced by statins in the early stages, but its protective role
fades over time.

An article
published this year in “Journal
of Nanabiotechnology” using one of our products,“Purified
Mouse Anti-Human CD9”, by our customers fromtheUniversidade da Coruña, DICOMOSA Group, Department
of Psychology, Area of Psychobiology, Edificio de Servicios Centrales de Investigación,
A Coruña, Spain, in how Toxicological assessment of silica-coated iron
oxide nanoparticles in human astrocytes. Congrats
and Thanks.

Summay:

Tumour-derived exosomes can be
released to serum and provide information on the features of the malignancy,
however, in order to perform systematic studies in biological samples, faster
diagnostic techniques are needed, especially for detection of low abundance
proteins. Most human cancer cells are positive for at least one ligand for the
activating immune receptor NKG2D and the presence in plasma of NKG2D-ligands
can be associated with prognosis.

Characterization of exosomes from metastatic melanoma cell lines. Exosomes from Ma-Mel-86c cells were purified from tissue culture supernatant by ultracentrifugation. a TEM. Exosomes were analyzed by electron microscopy. Bar: 100 nm. b Western blot. MICA and tetraspanins (CD63, CD81 and CD9) were analysed by Western blot. Actin was used as loading control. The result from a representative experiment is shown. An exposure of 10–15 s is shown in the right panel. c NKG2D downmodulation. Activated NK cells were co-incubated with increasing amounts of Ma-Mel-86c exosomes as indicated. Cells were stained with anti-NKG2D and analysed by flow cytometry. The plot represents the change in the mean fluorescence intensity (MFI) of NKG2D on NK cells after incubation with exosomes, related to NK cells incubated in medium alone. Data are the mean and SEM obtained in three experiments using NK cells from different donors (*P < 0.05)

An article
published this year in “Food
and Chemical Toxicology” using one of our products,“FITC AnnexinV
Apoptosis Detection Kit”, by our customers fromtheUniversidade da Coruña, DICOMOSA Group, Department
of Psychology, Area of Psychobiology, Edificio de Servicios Centrales de Investigación,
A Coruña, Spain, in how Toxicological assessment of silica-coated iron
oxide nanoparticles in human astrocytes. Congrats
and Thanks.

Summay:

Iron oxide nanoparticles (ION) have great potential for an increasing number of medical and
biological applications, particularly those focused on nervous system. Although ION seem
to be biocompatible and present low toxicity, it is imperative to unveil the
potential risk for the nervous system associated to their exposure, especially
because current data on ION effects on human nervous cells are scarce. Thus, in
the present study potential toxicity associated with silica-coated ION (S-ION)
exposure was evaluated on human A172 glioblastoma cells. To this aim, a
complete toxicological screening testing several exposure times (3 and 24 h),
nanoparticle concentrations (5–100 μg/ml), and
culture media (complete and serum-free) was performed to firstly assess S-ION
effects at different levels, including cytotoxicity – lactate
dehydrogenase assay, analysis of cell cycle and cell death production – and genotoxicity –
H2AX phosphorylation assessment, comet assay, micronucleus test and DNA repair competence assay. Results obtained showed that S-ION
exhibit certain cytotoxicity, especially in serum-free medium, related to cell
cycle disruption and cell death induction. However, scarce genotoxic effects
and no alteration of the DNA repair process were observed. Results obtained in
this work contribute to increase the knowledge on the impact of ION on the
human nervous system cells.

An article
published this year in “Redox
Biology” using one
of our products,“PE AnnexinV”, by our customers fromthe Instituto
de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain in how Protection against gamma-radiation injury by
protein tyrosine phosphatase 1B. Congrats
and Thanks.

Summay:

Protein tyrosine phosphatase 1B (PTP1B) is widely expressed in mammalian
tissues, in particular in immune cells, and plays a pleiotropic role in dephosphorylating many
substrates. Moreover, PTP1B expression is enhanced in response to pro-inflammatory stimuli and
to different cell stressors. Taking advantage of the use of mice deficient in
PTP1B we have investigated the effect of γ-radiation in
these animals and found enhanced lethality and decreased respiratory exchange
ratio vs. the
corresponding wild
type animals. Using bone-marrow
derived macrophages and mouse
embryonic fibroblasts (MEFs) from wild-type and PTP1B-deficient mice, we observed a
differential response to various cell stressors. PTP1B-deficient macrophages
exhibited an enhanced response to γ-radiation,
UV-light, LPS and S-nitroso-glutathione. Macrophages exposed to γ-radiation
show DNA
damage and
fragmentation, increased ROS production, a lack in GSH elevation and enhanced
acidic β-galactosidase activity. Interestingly, these differences were not observed in
MEFs. Differential gene expression analysis of WT
and KO macrophages revealed that the main pathways affected after irradiation
were an up-regulation of protein secretion, TGF-β signaling and
angiogenesis among other, and downregulation of Myc targets and Hedgehog signaling. These results demonstrate a key
role for PTP1B in the protection against the cytotoxicity of irradiation in
intact animal and in macrophages, which might be therapeutically relevant.

An article
published this year in “PlosOne”
using one of our products,“PerCP
Mouse anti-Human CD4”, by our
customers fromthe Immunology
Department, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain,
In how Levels of anti-CMV antibodies are
modulated by the frequency and intensity of virus reactivations in kidney
transplant patients. Congrats and Thanks.

Summay:

Anti-CMV (cytomegalovirus) antibody
titers are related to immune alterations and increased risk of mortality. To
test whether they represent a marker of infection history, we analyzed the
effect of viral reactivations on the production of specific antibodies in
kidney transplant patients. We quantified CMV-DNAemia and antibody titers in 58
kidney transplant patients before transplantation and during a follow-up of 315
days (standard deviation, SD: 134.5 days). In order to calculate the intensity
of the infection, we plotted the follow-up time of the infection on the x-axis
and the number of DNA-CMV copies on the y-axis and calculated the area under
the curve (CMV-AUC). The degree of T-lymphocyte differentiation was analyzed
with flow cytometry, the cells were labelled with different monoclonal
antibodies in order to distinguish their differentiation state, from naive
T-cells to senescent T-cells. Peak viremia was significantly higher in patients
experiencing a primary infection (VI) compared to patients experiencing viral
reactivation (VR). Our data indicate that the overall CMV viral load over the
course of a primary infection is significantly higher than in a reactivation of
a previously established infection. Whereas patients who experienced an episode
of CMV reactivation during the course of our observation showed increased
levels of CMV-specific antibodies, patients who did not experience CMV
reactivation (WVR) showed a drop in CMV antibody levels that corresponds to an
overall drop in antibody levels, probably due to the continuing
immunosuppression after the renal transplant. We found a positive correlation
between the CMV viremia over the course of the infection or reactivation and
the CMV-specific antibody titers in the examined patients. We also observed a
positive correlation between anti-CMV titers and T-cell differentiation. In
conclusion, our data show that anti-CMV antibody titers are related to the
course of CMV infection in kidney transplant patients.

Fig. Differentiation status of CD4+ and CD8+ T-lymphocytes according to CMV
serostatus and anti-CMV antibody levels.

(A)
Distribution of CD4+ and CD8+ T-cells into CD28+CD27+ (less-differentiated) and
CD28nullCD27null (more-differentiated) subsets
according to patients CMV serostatus. (B) Distribution of CD4+ and CD8+ T-cells
into CD28+CD27+ (less-differentiated), CD28+CD27null/CD28nullCD27+
(intermediate), and CD28nullCD27null (more-differentiated)
subsets was related to anti-CMV antibody titers in CMV-seropositive patients (n
= 24). Expression of CD28+ and CD27+ was analyzed by flow cytometry in gated
CD3+CD4+ T-cells and in CD3+CD8+ T-cells. Linear regression coefficients
adjusted by age and corresponding p-values are indicated

An article
published this year in “Dental
Materials” using one of our products,“PE Apoptosis Detection
kit”, by our customers fromtheHematopoietic Transplant
and Cellular Therapy Unit, Instituto Murciano de Investigación
Biosanitaria-Arrixaca, Virgen de la Arrixaca University Hospital, University of
Murcia, Murcia, Spain, In how Thermo-setting glass ionomer cements promote variable
biological responses of human dental pulp stem cells. Congrats and Thanks.

Summay:

Undiluted Equia Forte extracts led to a similar cell
proliferation rates than the
control group from 72h onwards. There were no significance differences between
Equia Forte and Ionostar Molar in terms of cell apoptosis and phenotype.
However, in presence of Equia extracts the migration capacity of hDPSCs was higher
than in presence of Ionostar Molar (p<0.05). Also, SEM studies showed a higher degree of cell attachment when
Equia Forte extracts were used. Finally, EDX analysis pointed to different
weight percentages of C, O and Ca ions in glass ionomer cements, while other elements such as La, Al, Si, W, Mo and F were
also detected.

Fig. 4. hDPSCs were cultured on Equia Forte, Ionostar Molar and plastic (control) for 72h, after which the cells were labelled with Annexin-V and 7-AAD and analysed by flow cytometry. Numbers within the different quadrants represent the percentages of live (Annexin-V−/7-AAD−), early apoptotic (Annexin-V+/7-AAD−) or late apoptotic and necrotic cells (Annexin-V+/7-AAD+ and Annexin-V−/7-AAD+). Dot-plots display representative flow cytometry results obtained after three independent experiments.